Vascular Impact of Dapagliflozin in CKD Patients (DAPAVASC)

NCT ID: NCT04930549

Last Updated: 2021-10-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

54 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-12-31

Study Completion Date

2023-03-31

Brief Summary

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This study aims to determine whether dapaglfiflozin 12-week administration is associated with a beneficial impact on the vasculature of patients with chronic kidney disease.

Detailed Description

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A prospective, randomized, double-blind studies evaluating the impact of once-daily dapagliflozin 10 mg versus placebo for 12 weeks on endothelial function, as primary endpoint, will be conducted in 56 patients with chronic kidney disease (eGFR ≥25 and ≤60 mL/min/1.73m2 by CKD-EPI) and without diabetes (fasting glycemia≥1.26 mg/dL, oral hypoglycemic agents or insulin) on top of standard treatment (n=27 per group). Indexes of arterial stiffness, cardiovascular coupling, cardiac function and plasma concentrations of endothelial, inflammatory and oxidative stress biomarkers will be assessed as secondary endpoints. Patients will be recruited in the Departments of Cardiology and Nephrology of Rouen University Hospital. The study will include an inclusion visit (V1), 2 exploration visits performed before (V2) and 12 weeks (V3) after treatment initiation, and 1 output study (V4).

Conditions

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Renal Insufficiency, Chronic

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Dapagliflozin 10Mg Tab

Dapagliflozin 10 mg film-coated tablets

Group Type EXPERIMENTAL

Dapagliflozin 10Mg Tab

Intervention Type DRUG

Patients receive dapagliflozin 10mg tablets once a day during 12 weeks

impedance cardiography

Intervention Type PROCEDURE

impedance cardiography (PhysioFlow® PF-05 Lab1TM, Manatec Biomedical) is done for evaluation of cardiac function

Applanation tonometry

Intervention Type PROCEDURE

Applanation tonometry will be done using SphygmoCor®, Hogimed) is done for evaluation of arterial stiffness

post-ischemic hyperemia of forearm

Intervention Type PROCEDURE

An arterial occlusion cuff will be placed on the forearm, and will be deflated to allow post-ischemic hyperemia with the continuous measurements of brachial artery diameter and blood flow velocity by high-resolution echotracking coupled to a Doppler system (ArtLab system®)

haemodynamics parameters

Intervention Type PROCEDURE

haemodynamics parameters will be evaluated using automatic oscillometric recorder

Placebo

Identical film-coated tablets without dapagliflozin

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Patients receive placebo tablets once a day during 12 weeks

impedance cardiography

Intervention Type PROCEDURE

impedance cardiography (PhysioFlow® PF-05 Lab1TM, Manatec Biomedical) is done for evaluation of cardiac function

Applanation tonometry

Intervention Type PROCEDURE

Applanation tonometry will be done using SphygmoCor®, Hogimed) is done for evaluation of arterial stiffness

post-ischemic hyperemia of forearm

Intervention Type PROCEDURE

An arterial occlusion cuff will be placed on the forearm, and will be deflated to allow post-ischemic hyperemia with the continuous measurements of brachial artery diameter and blood flow velocity by high-resolution echotracking coupled to a Doppler system (ArtLab system®)

haemodynamics parameters

Intervention Type PROCEDURE

haemodynamics parameters will be evaluated using automatic oscillometric recorder

Interventions

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Dapagliflozin 10Mg Tab

Patients receive dapagliflozin 10mg tablets once a day during 12 weeks

Intervention Type DRUG

Placebo

Patients receive placebo tablets once a day during 12 weeks

Intervention Type DRUG

impedance cardiography

impedance cardiography (PhysioFlow® PF-05 Lab1TM, Manatec Biomedical) is done for evaluation of cardiac function

Intervention Type PROCEDURE

Applanation tonometry

Applanation tonometry will be done using SphygmoCor®, Hogimed) is done for evaluation of arterial stiffness

Intervention Type PROCEDURE

post-ischemic hyperemia of forearm

An arterial occlusion cuff will be placed on the forearm, and will be deflated to allow post-ischemic hyperemia with the continuous measurements of brachial artery diameter and blood flow velocity by high-resolution echotracking coupled to a Doppler system (ArtLab system®)

Intervention Type PROCEDURE

haemodynamics parameters

haemodynamics parameters will be evaluated using automatic oscillometric recorder

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* Chronic kidney disease (eGFR ≥25 and ≤60 mL/min/1.73m² by CKD-EPI)
* Age ≥ 18 years
* Receiving a stable dose of an ACE inhibitor or ARB for at least 12 weeks before screening or patients who were documented to be intolerant to ACE inhibitors or ARBs

Exclusion Criteria

* Type 1 and type 2 diabetes (fasting glycemia≥126 mg/dL or use of oral hypoglycemic agents or insulin)
* Recessive or autosomal dominant polycystic kidney disease
* Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis
* Lupus nephritis
* Receiving cytotoxic therapy, immunosuppressive therapy or other immunotherapy for primary or secondary renal disease within 6 months prior to enrolment
* History of organ transplantation
* Body weight \> 35 kg/m²
* Receiving therapy with a sodium glucose co-transporter 2 (SGLT2) inhibitor within 8 weeks prior to enrolment or previous intolerance of an SGLT2 inhibitor
* Patients with NYHA class IV congestive heart failure at the time of enrolment
* Myocardial infarction, unstable angina, stroke or transient ischemic attack (TIA) within 12 weeks prior to enrolment
* Coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting) or valvular repair/replacement within 12 weeks prior to enrolment or is planned to undergo any of these procedures after randomization
* Active malignancy requiring treatment at the time of enrolment or is planned to undergo any treatment after randomization
* Severe hepatic impairment (Child-Pugh class C)
* History of frequent genital mycotic infections (\>2)
* Current pregnancy OR women of child-bearing potential (ie, those who are not chemically or surgically sterilized or who are not post-menopausal) who are not willing to use a medically accepted method of contraception that is considered reliable in the judgment of the investigator OR women who have a positive pregnancy test at enrolment or exploration visits OR women who are breast-feeding
* Contraindications to use glyceryl trinitrate (in particular allergy to nitrates or concomitant use of vasodilators)
* Participation in another clinical study with an investigational product during the last month prior to enrolment
* Inability of the patient, in the opinion of the investigator, to understand and/or comply with procedures and/or follow-up OR any conditions that, in the opinion of the investigator, may render the patient unable to complete the study.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role collaborator

University Hospital, Rouen

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Dominique Guerrot, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Rouen

Jeremy Bellien, PharmD, PhD

Role: STUDY_DIRECTOR

University Hospital, Rouen

Locations

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Department of Nephrology

Bois-Guillaume, , France

Site Status

Department of Pharmacology

Rouen, , France

Site Status

Countries

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France

Central Contacts

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Julien Blot

Role: CONTACT

+33232884035

Jeremy Bellien, MD, PhD

Role: CONTACT

+33232881428

Facility Contacts

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Dominique Guerrot, MD,PhD

Role: primary

+33232885446

Jeremy Bellien, PHarmD, PhD

Role: primary

+33232881428

Other Identifiers

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2021/0188/HP

Identifier Type: -

Identifier Source: org_study_id